home edit2 whole TSD November 2002 PDF format - OEHHA

Less-than-lifetime exposure induced statistically significant increased incidences of liver tumors in female
rats fed Aroclors 1260, 1254, and 1242 (Brunner et al., 1996). This result was most pronounced for
Aroclor 1260, where tumor incidences at the highest dose were higher for a 12-month exposure than
for a 24-month lifetime exposure. Only Aroclor 1016 showed no significant increases from less-thanlifetime
exposure. The earlier less-than-lifetime studies in rats and mice suggest that less-than-lifetime
exposure can quickly induce high incidences of early stages of tumor development (Kimbrough et al.,
1972; Ito et al., 1973, 1974). With further exposure, these can progress to malignancy (Kimbrough et
al., 1975; Norback and Weltman, 1985). Tumor incidences from less-than-lifetime exposure were
sometimes lower (Kimbrough and Linder, 1974), and sometimes similar (Rao and Banerji, 1988), to
those from full lifetime exposure to PCBs.
Infants can be highly exposed to PCBs during pregnancy and lactation (Dewailly et al., 1991, 1994).
The accumulation of PCBs in human adipose tissue creates a store for subsequent release of PCBs into
the bloodstream and then into the fetal circulation. During the postpartum period, PCBs are mobilized
from adipose stores, transferred into human milk, and delivered to the neonate via nursing (Dewailly et
al., 1991). This pathway may account for a substantial fraction of neonatal exposure to dioxin-like and
other PCBs.
Additionally, normal fetal development depends on the timing and rate of release of T3 and T4. Some
evidence indicates that PCBs can alter normal T3 and T4 metabolism, thereby disturbing thyroid
function and provoking secondary impacts on organogenesis during development. Any estrogenic/antiestrogenic,
androgenic/anti-androgenic, or other hormonal activity of PCB mixtures has the possibility of
altering the development of reproductive organs or the urogenital tract, potentially causing cancer or
other adverse effects through a mechanism different from those causing liver cancer (US EPA, 1996b).
Few studies, however, have investigated early-life sensitivity. In human infants, glucuronidative
mechanisms are not fully developed; additionally, some nursing infants receive a steroid in human milk
that inhibits the activity of glucuronyl transferase, further reducing PCB metabolism and elimination
(Calabrese and Sorenson, 1977). In animals, Aroclor 1260 induced high incidences of liver tumors
when fed to 5-week-old rats for a short time (Rao and Banerji, 1988). On the other hand, acute
perinatal dosing with Aroclor 1254 promoted nitrosamine-initiated lung and liver tumors in mice but did
not induce cancer in the offspring when administered alone (Anderson et al., 1983, 1986, 1994). A
study of polybrominated biphenyls (PBBs) found that perinatal exposure enhanced susceptibility to liver
tumors for female rats also exposed as adults and increased the incidence of liver tumors in male and
female mice not further exposed as adults (NTP, 1993). Because of the potential magnitude of earlylife
exposures, the possibility of greater perinatal sensitivity, and the likelihood of interactions among
thyroid and hormonal development, it is reasonable to conclude that early-life exposures may be
associated with increased risks; this would indicate using the "high-risk" potency estimates for early-life
exposure.
US EPA has listed three different cancer potency values for PCBs; the choice of which factor to use
depends on the physical form of the PCBs and the expected route of exposure. However, US EPA
states that the "high risk and persistence" factor (2.2 (mg/kg-day) -1 ) should be used when an "early-life
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